Depo-Provera - instructions for use, dose, side effects, contraindications

Excipients: sodium chloride 8.6 mg, methylparahydroxybenzoate 1.35 mg, propyl parahydroxybenzoate 0.15 mg, polysorbate 80 2.4 mg, macrogol 3350 28.5 mg, water for injection q.s. up to 1 ml.

Description:

White homogeneous suspension without visible inclusions after mixing.

Pharmacotherapeutic group:Gestagen

ATX: & nbsp

L.02.A.B.02 Medroxyprogesterone

L.02.A.B Progestogens

Pharmacodynamics:

Medroxyprogesterone acetate (MPA), a synthetic derivative of progesterone, refers to progestins that do not possess estrogenic activity and has the following pharmacological effect on the endocrine system:

- inhibits the secretion of pituitary gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH));

- reduces the concentration of adrenocorticotropic hormone (ACTH) and hydrocortisone in the blood plasma;

- Suppresses the function of Leydig cells in men and reduces the concentration of testosterone in the blood plasma;

- reduces the concentration of estrogens in the blood plasma (by inhibiting the secretion of FSH, as well as the enzymatic induction of hepatic reductase, which leads to an increase in testosterone clearance and the subsequent decrease in the conversion of androgens to estrogens).

The antitumor effect of the drug in therapeutic doses in the treatment of hormone-dependent malignant neoplasms may be due to its effect on the hypothalamic-pituitary-gonadal system, the receptors of progestins and estrogens, and the metabolism of sex hormones at the cellular level.

IPA, as well as progesterone, has a pyrogenic effect. At very high doses, used for the therapy of certain cancers (500 mg per day or more), the development of the Itenko-Cushing symptom complex is possible.

Pharmacokinetics:

After intramuscular (IM) administration of MPA it release occurs slowly, which ensures the creation of low, but constant concentrations of MPA in the blood plasma. The time to reach the maximum concentration after a / m injection is about 4-20 days.MPA can be detected in the blood plasma even after 7-9 months after the IM injection. More than 90% of MPA is in the blood plasma in associated with proteins state (mainly with albumin). IPA does not bind to a specific globulin that binds sex hormones. Unbound IPA also has pharmacological activity.

Scope allocation of is 20 ± 3 liters. MPA penetrates through the blood-brain barrier, the placenta and into breast milk.

IPA to a large extent is metabolized with the participation of cytochrome P450 3A4 in liver microsomes by hydroxylation followed by conjugation. At present, no less than 16 metabolites of MPA are known. Most of is displayed through the intestines by biliary secretion. About 30% of the total dose is displayed kidneys 4 days after IM injection in the form of glucuronides and only a small part - in the form of sulfates. The half-life period after the / m administration is 6 weeks.

Indications:

- Relapses and / or metastases of breast cancer.

- Relapses and / or metastases of endometrial cancer.

- Relapses and / or metastases of kidney cancer.

- Metastatic prostate cancer.

Contraindications:

- Hypersensitivity to MPA or any other component of the drug;

- bVariability and the period of breastfeeding (during the first 6 weeks of the postpartum period);

- tovomiting from the vagina;

- atmarked violations of the liver;

- PThe injection of the MPA is contraindicated prior to the onset of menarche.

Carefully:

Thrombophlebitis, thromboembolic complications and stroke (increased risk of developing or in anamnesis), epilepsy, migraine, bronchial asthma, heart failure, diabetes, depressive states.

Pregnancy and lactation:

MPA is contraindicated in pregnancy.

There are reports that under certain conditions, there is a correlation between the intrauterine exposure of progestogens during the first trimester of pregnancy and the developmental disorders of the genitals in the fetus.

Newborns, in the case of an unplanned pregnancy occurring within 1-2 months after the injection of MPA, have a greater risk of developing hypotrophy, which in turn increases the risk of intrapartum and neonatal mortality. The risk of developing such complications is relatively low, since pregnancy is rare when using MPA.

In the event that pregnancy has developed against the background of the use of MPA, the patient should be warned about the possible risk to the fetus.

MPA is excreted in breast milk. There is no evidence that this may cause any harm to the newborn breastfed. However, the use of MPA in the first six weeks of the postpartum period is not recommended.

Dosing and Administration:

DEPOSITORY is entered intramuscularly.

BREAST CANCER: 500-1000 mg per day for 28 days; then switch to a maintenance dose of 500 mg twice a week. If signs of progression appear, treatment with the drug is canceled.

CANCER ENDOMETRY AND CANCER CANCER: initial dose of 400-1000 mg per week; if within a few weeks or months there has come an improvement and stabilization of the process is achieved, then it is possible to switch to maintenance therapy - 400 mg per month.

Metastatic prostate cancer: an initial dose of 500 mg 2 times a week for 3 months, maintaining a dose of 500 mg once a week.

Application for renal failure

In clinical trials, there was no change in the pharmacokinetics of MPA in patients with renal insufficiency.Since MPA is excreted exclusively by metabolism in the liver, this category of patients does not require dose adjustment.

Application for violations of liver function

In clinical studies, there was no change in the pharmacokinetics of MPA in patients with hepatic insufficiency. However, since MPA is excreted by metabolism in the liver, sex hormones can be very poorly metabolized in patients with severe hepatic insufficiency (see section "Contraindications").

Immediately before use, the vial should be shaken well to allow the drug to form a homogeneous suspension.

Side effects:

All unwanted reactions are listed with the distribution by class and frequency: very often (> 1/10), often (> 1/100 to <1/10), infrequently (> 1/1000 to <1/100), rarely (<1 / 1000), the frequency is unknown - it is impossible to estimate the frequency based on the available data.

System-Organ Class	Unwanted drug reactions
Disorders from the hematopoiesis system
Frequency unknown	An increase in the number of leukocytes and platelets in the blood plasma.
Disorders from the endocrine system
Often	Change in body weight.
Infrequently	Decompensation of diabetes mellitus, symptomatic complex Itenko-Cushing (obesity, lunar face, osteoporosis, menstrual cycle disorder, stria of different color, hirsutism, edema on the lower extremities, decreased sexual function, hyperpigmentation of skin in places of friction, hypokalemia).
Rarely	Decreased glucose tolerance.
Frequency unknown	Glucosuria, galactorrhea.
Disorders from the genitourinary system
Often	Erectile disfunction.
Infrequently	Dysfunctional uterine bleeding (irregular, abundant, scanty, changing libido, changing libido, smearing), mastodynia, soreness of the breast or mammary glands, changes in libido.
Frequency unknown	Amenorrhea, prolonged anovulation, erosion of the cervix, changes in discharge from the vagina, abdominal pain, vaginitis, hypersensitivity of the nipples of the breast or mammary glands.
Disturbances from the nervous system
Often	Insomnia, dizziness, headache, fatigue, tremors of the hands.
Infrequently	Euphoria, depression, cramps calf muscles at night.
Rarely	Increased nervous excitability, drowsiness.
Frequency unknown	Confusion, decreased ability to concentrate, reactions like adrenergic, tonic or clonic convulsions.
Disorders from the cardiovascular system
Infrequently	Chronic heart failure, thrombophlebitis, thromboembolism of the pulmonary artery.
Rarely	Stroke, myocardial infarction, thromboembolic disorders, increased blood pressure.
Frequency unknown	Attacks of palpitation, tachycardia, sensation of "tides".
Disturbances on the part of the organ of sight
Frequency unknown	Diabetic cataract, visual disturbances, thrombosis of the retina.
Disturbances from the digestive system
Often	Constipation, nausea, vomiting, changes in appetite.
Infrequently	Diarrhea, dryness of the oral mucosa.
Rarely	Jaundice.
Frequency unknown	Violation of the liver, pain and discomfort in the abdomen, flatulence.
Disturbances from the skin and skin appendages
Often	Sweating.
Infrequently	Acne, hirsutism.
Rarely	Alopecia, rash.
Frequency unknown	Acquired lipodystrophy, hives, itching.
Disturbances from musculoskeletal and connective tissue
Infrequently	Spasm of muscles
Immune system disorders
Infrequently	Angioedema.
Rarely	Hypersensitivity reactions.
Frequency unknown	Anaphylaxis and anaphylactoid reactions.
Other
Often	Reactions at the injection site (compaction at the injection site, skin discoloration at the injection site, sterile abscess), swelling / fluid retention in the body.
Infrequently	Pain / hypersensitivity at the injection site, hypercalcemia.
Rarely	Misery, hyperthermia.
Frequency unknown	Persistent atrophy at the injection site, the formation of a depression at the injection site, compaction at the injection site, back pain and joint pain.

When using the drug after its registration, rare cases of osteoporosis, including osteoporotic fractures of bones, were recorded.

Overdose:

The use of very high doses of the drug can cause a number of symptoms, including an increase in body weight (with some fluid retention), increased fatigue, and in some cases, effects characteristic of glucocorticosteroids.

In case of accidental overdose, discontinue use. Specific treatment is not required.

Interaction:

When combined aminoglutethimide can significantly reduce the concentration of MPA in the blood plasma and thereby reduce its effectiveness.

IPA in vitro metabolized predominantly by hydroxylation via the CYP3A4 isoenzyme. Special studies of the effect of inhibitors or inducers of the isoenzyme CYP3A4 on the pharmacokinetics of MPA have not been conducted. In connection with the high probability of such interaction, it is theoretically possible to assume the effect on the efficiency of MPA. However, the clinical effects of simultaneous use of inhibitors or inducers of the isoenzyme CYP3A4 and MPA are unknown.

Special instructions:

The drug is used strictly according to prescription and under the supervision of a doctor.

- If dysfunctional uterine bleeding occurs, the patient should be examined to determine the etiology.

- During the period of therapy with the drug DEPO-PROVER, it is necessary to carefully monitor the condition of patients who were previously treated for depression.

- When treating patients with diabetes should take into account the ability of MPA to reduce glucose tolerance.

- If it is necessary to cytologic or histological study of the endometrium or cervix, the pathologist should be warned about the therapy with the DEPO-CHECK drug.

- When conducting laboratory studies, it should be borne in mind that the use of MPA can alter the concentrations of the following endocrine biomarkers:

a) Steroids in blood plasma and urine (cortisol, estrogens, pregnanediol, progesterone, testosterone);

b) gonadotropins in blood plasma and urine (LH and FSH);

c) a specific globulin that binds the sex hormones.

- In some patients receiving MPA, suppression of the function of the adrenal cortex (decrease in the concentration of ACTH and hydrocortisone in the blood plasma) was detected.

- When conducting the metapyrone test, it should be borne in mind that high doses of MPA used in oncology can cause partial adrenal insufficiency (a decrease in the response of the pituitary-adrenal system), therefore, before the metapirone is introduced, it is necessary to check the ability of the suprarenal cortex to respond to ACTH.

- It is necessary to interrupt the use of the drug and to conduct a test with sudden partial or complete loss of vision, or with the development of exophthalmos, double vision, migraine attacks. When revealing damage to the vessels of the retina or edema of the optic nerve disc, treatment with the drug should be discontinued.

- Despite the fact that there was no causal relationship between the use of MPA and the development of thromboembolic disorders, in patients with these disorders in the history or when they occur against the background of treatment, the use of the drug DEPO-CHECK.

- The effect of using the drug in high doses on bone density (PCT) has not been studied. The decrease in the concentration of estrogens in blood plasma, caused by the use of the drug, leads to a decrease in PCT in women before menopause and may increase the risk of osteoporosis in subsequent years of life. All patients who use the drug DEPO-CHECK, it is recommended to take calcium and vitamin preparations D (in the absence of contraindications), and with prolonged use - periodically measure PBC.

Effect on the ability to drive transp. cf. and fur:The effect of the drug on the ability to drive vehicles and mechanisms has not been studied, but it must be taken into account that DEPO-PROVERE® can cause dizziness and visual impairment, therefore, when taking the drug, care must be taken when performing the above actions.

Form release / dosage:Suspension for intramuscular injection, 150 mg / ml.

Packaging:Pabout 3.3 ml (500 mg MPA) and 6.7 ml (1000 mg MPA) in bottles of transparent colorless glass of class I (Hebrew Pharm.), sealed with butyl rubber stoppers, coated with aluminum caps, with plastic removable protective caps; 1 bottle with the instruction for use is placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013671 / 01

Date of registration:30.12.2011

Expiration Date:Unlimited

The owner of the registration certificate:Pfizer IFG Belgium N.V.Pfizer IFG Belgium N.V. Belgium

Manufacturer: & nbsp

PFIZER MFG. BELGIUM, N.V. Belgium

Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation

Information update date: & nbsp23.04.2017

Illustrated instructions

Instructions

Depo-Provera (Depo-Provera)